C3435T polymorphism of the ABCB1 gene: impact on genetic susceptibility to peptic ulcers

Abstract

The functional single nucleotide polymorphism (SNP) C3435T in exon 26 of the ABCB1 gene encoding the xenobiotic transporter P-glycoprotein (P-gp) may influence susceptibility to several diseases, as well as the clinical outcome of treatment with P-gp substrates. Exposure to environmental chemicals is thought to be involved in peptic ulcer pathogenesis and then later in stomach cancer development. About 80% of ulcers are associated with Helicobacter pylori infection, one of the risk factors of stomach cancer. P-gp-transported drugs are used in treatment of H. pylori. Therefore, a lack of effectiveness in eradication therapy can lead to chronic stomach inflammation and promote cancerogenesis. In this study, 196 patients with peptic ulcers divided into two groups with and without H. pylori infection and combined with 96 healthy controls were genotyped for the ABCB1 C3435T SNP. A trend towards higher incidence of the 3435TT genotype among peptic ulcer patients than in controls (p = 0.0983) was observed. Likewise, the 3435T allele was more frequent in groups suffering from peptic ulcers. The association was near to statistical significance (p = 0.0538). Between analyzed genotypes and H. pylori infection, statistically significant dependence was found (p = 0.0372). In addition, the CT genotype was associated with 1.56 times and the TT with 2.45 times higher prevalence of infection compared to the CC genotype. Asimilar association was present in a subgroup of peptic ulcer men (p = 0.0090). The isolated C3435T ABCB1 SNP is not a major factor for genetic susceptibility to peptic ulcer, but in a group of men who suffered from peptic ulcer, this polymorphism seemed to be a risk factor for H. pylori infection development.

Investigation ofABCB11236 and 2677 SNPs in patients with peptic ulcer

“…In the study group, mutant homozygosity for both 1236 and 2677 SNPs was found to be connected with a much higher risk of the disease compared with wild-type homozygosity, 2.03 and 1.71 times higher respectively. This is in agreement with the results from previous research where only one polymorphism in position 3435 was checked and a trend toward higher incidence of the 3435TT genotype among peptic ulcer patients than controls was observed (p = 0.0983) [14].…”

“…TT homozygous women were proved to have 1.66 times greater risk of H. pylori infection than CC women carriers. That corroborates previous results where a statistically significant dependence was reported between TT genotype for the 3435 SNP of ABCB1 gene and H. pylori infection [14].…”

“…This is a silent mutation, the binding of which altered protein function [13] and was previously investigated by the authors of this study in the same population of patients with peptic ulcer. The trend toward higher incidence of the 3435TT genotype among peptic ulcer patients than controls was observed [14].…”

P‐glycoprotein expression in Helicobacter pylori‐positive patients: The influence of MDR1 C3435T polymorphism

“…However, Sugimoto et al 14 . reported that there was no relationship between the MDR1 C3435T polymorphism and the risk of developing H. pylori ‐related gastric cancer or peptic ulcer, and another report 15 suggested that genotypes of CT and TT increased the prevalence of H. pylori infection compared with the CC genotype.…”

Investigation of -308G>A and -1031T>C Polymorphisms in the TNFA Promoter Region in Polish Peptic Ulcer Patients

“…Recently, we showed that 3435C>T polymorphism of the ABCB1 gene is a risk factor for H. pylori infection development in male peptic ulcer patients but not in female peptic ulcer patients 26. Due to a significant overrepresentation of female in the investigated cohort of patients (women to men ratio, 1.68), analysis was performed in subgroups of women and men.…”